2.1. BLOOD TRANSFUSIONS AND TRANSFUSION REACTIONS
Blood transfusions are used to supplement the hemodynamic system of patients who suffer from a variety of disorders, including diminished blood volume, or hypovolemia (e.g. due to bleeding), a decreased number of blood cells (e.g. due to bone marrow destruction), or impaired or damaged blood cells (e.g. due to hemolytic anemia). Blood transfusions serve not only to increase the intravascular volume, but also to supply red blood cells which carry dissolved oxygen and facilitate oxygen delivery to tissues.
Often, the critical need for a blood transfusion arises acutely. In a previously healthy person, an acute blood loss of as much as 10 percent of the normal blood volume (i.e. about 500 ml) may be compensated for by a constriction of the arteriolar bed and an augmentation in heart rate; however, when blood volume is reduced by 15 to 25 percent (i.e. about 750 to 1250 ml), cardiac output falls markedly. Thereafter, relatively small losses of blood may result in life-threatening reductions of cardiac output, blood pressure, and tissue perfusion. Reduced delivery of oxygen to tissues promotes anaerobic glycolysis, and plasma lactate levels rise (Braunwald and Williams, 1983, in "Harrison's Principles of Internal Medicine", Petersdorf et al., eds. McGraw-Hill Book Company, N.Y., p. 173). It is essential that an adequate blood replacement be immediately available in such situations.
Currently, a number of intravenous fluids are available for the treatment of acute hypovolemia, including crystalloids, such as lactated Ringer's solution or normal saline, and colloidal solutions, such as normal human serum albumin. Crystalloids and colloids temporarily correct the volume deficit, but do not directly supplement oxygen delivery to tissues. Blood transfusion is the preferred mode of treatment; however, there is often a time lag before the blood transfusion may be ordered and administered. Frequently, the patient's exact blood type needs to be determined before donated blood can be ordered. May, in "Emergency Medicine" (1984, John Wiley & Sons, Publ., NY, p. 263) comments that, for the critically injured patient, "(t)he type of blood that is given usually depends on the availability in the blood bank at the time." Unfortunately, the amount and variety of blood available for transfusions is inconsistent and unpredictable; for rare blood types, availability is a perpetual problem.
In addition to problems of availability, blood transfusions are associated with a number of clinical complications, which may broadly be classified as immune or non-immune reactions. Among the immunological transfusion reactions is hemolysis (lysis of red blood cells) due to red blood cell alloantibodies, which may occur intravascularly or extravascularly. Extravascular hemolysis is typically associated with antibodies of the Rh system, but several additional antibodies may also be involved (for example, antibodies reactive with antigens of the Kell, Duffy and Kidd systems). Clinical symptoms are generally relatively mild, consisting of malaise and fever. Intravascular hemolysis, however, usually due to incompatibility within the ABO system, is associated with a more severe clinical syndrome, including restlessness, anxiety, flushing, chest or lumbar pain, tachypnea, tachycardia, and nausea, often followed by shock and renal failure (Giblett, in "Harrison's Principles of Internal Medicine, "Petersdorf, et al eds. McGraw-Hill Book Co., N.Y., p. 1915).
Transfusion of non-irradiated blood products has been associated with acute graft versus host disease in immunocompromised patients (von Fliedner et al., 1982, Am. J. Med. 72:951-961; Brubaker, 1986, Hum. Pathol. 17:1085-1088; Kessinger et al., 1987, J. Surg. Oncol. 36:206-209). Recently, however, two cases of fatal transfusion-associated graft versus host disease were reported in immunocompetent patients after cardiac surgery (Thaler et al., 1989, N. Engl. J. Med. 321:25-28).
Non-immune transfusion reactions include circulatory overload (especially in patients with renal or cardiac insufficiency), infections, metabolic disturbances, air and fat embolisms, thrombophlebitis, and siderosis. Massive transfusion can result in hyperkalemia, ammonia and citrate toxicity, which may be avoided by using blood stored for no more than a week, and dilutional coagulopathies, which may be obviated by supplementation with platelet concentrates. Siderosis may result from exposure to free iron from hemolyzed blood (Giblett, in "Harrison's Principles of Internal Medicine," Petersdorf et al., eds. McGraw-Hill Book Co., N.Y., p. 1915).
Infections associated with blood transfusions include hepatitis (especially non-A, non-B), cytomegalovirus infection, syphilis, malaria, toxoplasmosis, brucellosis, acquired immune deficiency syndrome (AIDS), and adult T cell leukemia. Beginning in March 1985, voluntary deferral of blood donation by persons at risk for human immunodeficiency virus (HIV) and screening of donated units for HIV-1 antibody have reduced the risk of transfusion-related HIV infection (Ward et al., 1986, JAMA 256:357-361; Ward et al., 1988, N. Engl. J. Med. 318:473-478). However, rare cases of HIV transmission by pre-screened blood components has been reported (MMWR, 1986, 35:389-391). Imagawa et al. (1989, N. Engl. J. Med. 320:1458-1462) reported the isolation of infectious HIV-1 virus from 31 of 133 high-risk individuals who tested negative for antibodies on conventional ELISA and Western blot assay. Further, the screening of donated blood units for antibodies to HTLV-I (the causative agent of a form of human T cell leukemia) has recently been recommended by the FDA (MMWR, 1988, 37:736-747). Cohen et al. (1989, N. Engl. J. Med. 320:1172-1176) reported that the observed risk of HIV-1 transmission was .003 percent per unit of blood; the risk of HTLV-I infection was found to be 0.024 percent per unit of blood transfused.